Authors :
Presenting Author: Karl Hansen, PhD – Praxis Precision Medicines
Bashar Mohsen, MD – Assertive Research Center, Miami
Noam Epstein, MD – Praxis Precision Medicines
Maribel Hernandez, PA-C – Praxis Precision Medicines
Megan Sniecinski, BS, MBA – Praxis Precision Medicines
Kimberly Crimin, PhD – Praxis Precision Medicines
Minao Tang, PhD – Praxis Precision Medicines
Steven Petrou, PhD – Praxis Precision Medicines
Marcio Souza, PharmD, MBA – Praxis Precision Medicines
Orrin Devinsky, MD – NYU Comprehensive Epilepsy Center, NYU Langone Medical Center
Ángel Aledo-Serrano, MD – Epilepsy Unit, Clinical Neuroscience Institute, Vithas Madrid University Hospitals
Rationale:
Epilepsy affects ~3.5 million individuals in the US with a significant proportion experiencing uncontrolled seizures despite treatment with multiple antiseizure medications (ASMs). While sodium channel blockers (SCBs) are among the most effective ASMs, approved medications lack sufficient efficacy or have dose-limiting side effects. Vormatrigine is a functional state modulator precisely targeting the hyperexcitable state of sodium channels in the brain, and is in development for adult focal onset seizures (FOS) and generalized epilepsy. The RADIANT study was designed to evaluate vormatrigine’s efficacy, safety, and pharmacokinetics in adults with FOS or idiopathic primary generalized tonic-clonic seizures (PGTS).
Methods:
RADIANT (NCT06908356) is a Phase 2 clinical trial enrolling up to 80 participants aged 18-75 years with FOS or idiopathic PGTS based on the ILAE classification. Participants received vormatrigine 30mg daily for 8 weeks, with the study consisting of Screening/Observation (Baseline), Treatment and Follow-up periods. The primary endpoint was median percent change in monthly (28 day) seizure frequency from Baseline to Week 8. Topline results are presented for the initial evaluable cohort of 37 subjects with focal epilepsy.
Results:
The overall median percent reduction in focal seizure frequency from baseline to Week 8 was 56.3% (Wilcoxon signed-rank test p< 0.05 for each weekly comparison and overall). The overall response rate during the treatment period was ~60%, with more than 20% of participants achieving seizure freedom during the last month of treatment. Participants experienced a rapid onset of efficacy, which progressively increased from Week 1 through Week 8; with 54% achieving ≥ 50% response in the first week and 67% in Week 8.